IL271680B - Compositions and methods for inhibiting hmgb1 expression - Google Patents
Compositions and methods for inhibiting hmgb1 expressionInfo
- Publication number
- IL271680B IL271680B IL271680A IL27168019A IL271680B IL 271680 B IL271680 B IL 271680B IL 271680 A IL271680 A IL 271680A IL 27168019 A IL27168019 A IL 27168019A IL 271680 B IL271680 B IL 271680B
- Authority
- IL
- Israel
- Prior art keywords
- oligonucleotide
- seq
- nucleotides
- set forth
- hmgb1
- Prior art date
Links
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
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- C—CHEMISTRY; METALLURGY
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| PCT/US2018/040410 WO2019006375A1 (en) | 2017-06-29 | 2018-06-29 | COMPOSITIONS AND METHODS FOR INHIBITING HMGB1 EXPRESSION |
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| IL295086A IL295086A (en) | 2017-06-29 | 2018-06-29 | Compositions and methods for inhibiting expression of hmgb1 |
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| US10675295B2 (en) | 2017-06-29 | 2020-06-09 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting HMGB1 expression |
| CN111971051A (zh) * | 2018-04-13 | 2020-11-20 | 迪克纳制药公司 | 用增加tm的核苷酸修饰的双链核酸抑制剂分子 |
| JP7535047B2 (ja) * | 2018-12-12 | 2024-08-15 | ディセルナ ファーマシューティカルズ インコーポレイテッド | トリループを含む二本鎖核酸インヒビター分子 |
| IL284327B2 (en) * | 2018-12-28 | 2024-11-01 | Dicerna Pharmaceuticals Inc | Compositions and methods for inhibiting hmgb1 expression |
| KR20230171431A (ko) * | 2021-04-14 | 2023-12-20 | 다이서나 파마수이티컬, 인크. | Pnpla3 발현을 조절하기 위한 조성물 및 방법 |
| IL307154A (en) * | 2021-04-19 | 2023-11-01 | Novo Nordisk As | Compositions and methods for inhibiting nuclear receptor subfamily 1 group h member 3 (nr1h3) expression |
| CN117280031A (zh) * | 2021-04-19 | 2023-12-22 | 诺和诺德股份有限公司 | 用于抑制核受体亚家族1组h成员3（nr1h3）表达的组合物和方法 |
| KR20240046843A (ko) * | 2021-08-25 | 2024-04-11 | 노보 노르디스크 에이/에스 | 알파-1 항트립신 발현을 억제하기 위한 조성물 및 방법 |
| JP7877458B2 (ja) * | 2021-12-01 | 2026-06-22 | ディセルナ ファーマシューティカルズ インコーポレイテッド | Ａｐｏｃ３発現を調節するための組成物及び方法 |
| TWI868755B (zh) * | 2022-06-24 | 2025-01-01 | 丹麥商諾佛 儂迪克股份有限公司 | 抑制跨膜絲胺酸蛋白酶６（ｔｍｐｒｓｓ６）表現的組成物及方法 |
| CN117264954A (zh) * | 2022-09-20 | 2023-12-22 | 北京福元医药股份有限公司 | 用于抑制hmgb1基因表达的双链核糖核酸及其修饰物、缀合物和用途 |
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| EP2617426A1 (en) * | 2010-09-17 | 2013-07-24 | Japan Science and Technology Agency | Inhibitor of hmgb protein-mediated immune response activation, and screening method |
| WO2016100401A1 (en) * | 2014-12-15 | 2016-06-23 | Dicerna Pharmaceuticals, Inc. | Ligand-modified double-stranded nucleic acids |
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| US7250496B2 (en) * | 2002-11-14 | 2007-07-31 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
| US20080311122A1 (en) | 2005-11-28 | 2008-12-18 | Medimmune, Llc | Antagonists of Hmgb1 and/or Rage and Methods of Use Thereof |
| US8178503B2 (en) * | 2006-03-03 | 2012-05-15 | International Business Machines Corporation | Ribonucleic acid interference molecules and binding sites derived by analyzing intergenic and intronic regions of genomes |
| US20110081362A1 (en) * | 2008-01-31 | 2011-04-07 | The Brigham And Women's Hospital, Inc. | Treatment of cancer |
| WO2010033225A2 (en) * | 2008-09-22 | 2010-03-25 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for the specific inhibition of gene expression by dsrna possessing modifications |
| WO2011007876A1 (ja) * | 2009-07-16 | 2011-01-20 | Ｎｅｃソフト株式会社 | Ｈｍｇｂ１結合核酸分子およびその用途 |
| WO2014028494A1 (en) * | 2012-08-13 | 2014-02-20 | The Regents Of The University Of California | Detecting and treating liver damage |
| US10351854B2 (en) * | 2014-10-10 | 2019-07-16 | Dicerna Pharmaceuticals, Inc. | Therapeutic inhibition of lactate dehydrogenase and agents therefor |
| WO2017079227A1 (en) * | 2015-11-05 | 2017-05-11 | University Of Connecticut | Compositions and methods for the treatment of liver fibrosis |
| CN106244589A (zh) * | 2016-08-01 | 2016-12-21 | 中国人民解放军第四军医大学 | 靶向hmgb1基因的rna干扰片段及其应用 |
| US10675295B2 (en) | 2017-06-29 | 2020-06-09 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting HMGB1 expression |
| WO2019126097A1 (en) * | 2017-12-18 | 2019-06-27 | Alnylam Pharmaceuticals, Inc. | High mobility group box-1 (hmgb1) irna compositions and methods of use thereof |
| US11883019B2 (en) | 2017-12-21 | 2024-01-30 | Cilag Gmbh International | Stapling instrument comprising a staple feeding system |
| IL284327B2 (en) | 2018-12-28 | 2024-11-01 | Dicerna Pharmaceuticals Inc | Compositions and methods for inhibiting hmgb1 expression |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2617426A1 (en) * | 2010-09-17 | 2013-07-24 | Japan Science and Technology Agency | Inhibitor of hmgb protein-mediated immune response activation, and screening method |
| WO2016100401A1 (en) * | 2014-12-15 | 2016-06-23 | Dicerna Pharmaceuticals, Inc. | Ligand-modified double-stranded nucleic acids |
Non-Patent Citations (1)
| Title |
|---|
| GE, WEN-SONG, ET AL., INHIBITION OF HIGH-MOBILITY GROUP BOX 1 EXPRESSION BY SIRNA IN RAT HEPATIC STELLATE CELLS., 31 December 2011 (2011-12-31) * |
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| EP3645013A4 (en) | 2021-07-21 |
| IL295086A (en) | 2022-09-01 |
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| CN111050776A (zh) | 2020-04-21 |
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